Jump to main content
Jump to site search

Issue 4, 2017
Previous Article Next Article

A specific fluorescent probe reveals compromised activity of methionine sulfoxide reductases in Parkinson's disease

Author affiliations

Abstract

Oxidation of methionine residues to methionine sulfoxide (MetSO) may cause changes in protein structure and function, and may eventually lead to cell damage. Methionine sulfoxide reductases (Msrs) are the only known enzymes that catalyze the reduction of MetSO back to methionine by taking reducing equivalents from the thioredoxin system, and thus protect cells from oxidative damage. Nonetheless, a lack of convenient assays for the enzymes hampers the exploration of their functions. We report the discovery of Msr-blue, the first turn-on fluorescent probe for Msr with a >100-fold fluorescence increment from screening a rationally-designed small library. Intensive studies demonstrated the specific reduction of Msr-blue by the enzymes. Msr-blue is ready to determine Msr activity in biological samples and live cells. Importantly, we disclosed a decline of Msr activity in a Parkinson's model, thus providing a mechanistic linkage between the loss of function of Msrs and the development of neurodegeneration. The strategy for the discovery of Msr-blue would also provide guidance for developing novel probes with longer excitation/emission wavelengths and specific probes for Msr isoforms.

Graphical abstract: A specific fluorescent probe reveals compromised activity of methionine sulfoxide reductases in Parkinson's disease

Back to tab navigation

Supplementary files

Publication details

The article was received on 21 Oct 2016, accepted on 25 Jan 2017 and first published on 27 Jan 2017


Article type: Edge Article
DOI: 10.1039/C6SC04708D
Citation: Chem. Sci., 2017,8, 2966-2972
  • Open access: Creative Commons BY license
  •   Request permissions

    A specific fluorescent probe reveals compromised activity of methionine sulfoxide reductases in Parkinson's disease

    L. Zhang, S. Peng, J. Sun, J. Yao, J. Kang, Y. Hu and J. Fang, Chem. Sci., 2017, 8, 2966
    DOI: 10.1039/C6SC04708D

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements